Culture

Signal peptides' novel role in glutamate receptor trafficking and neural synaptic activity

Glutamate is the major excitatory neurotransmitter in the brain, and the postsynaptic expression level of glutamate receptors is a critical factor in determining the efficiency of information transmission and the activity of the neuronal network. Therefore, glutamate receptor trafficking is critical to the physiological function of human brain circuitry.

It is known that KAR-type glutamate receptors are closely related to many neurological disorders. Dr. SHENG Nengyin at the Kunming Institute of Zoology of the Chinese Academy of Sciences has long been devoted to studying the regulation of KAR trafficking. His previous studies have revealed that in neurons the trafficking performance of KAR subunits GluK1 and GluK2 are totally different, and it is the amino acid sequences of their extracelluar domains that determine their distinct trafficking capability.

To resolve the molecular machinery, the "Neural Synaptic Mechanism and Function" group led by Dr. SHENG Nengyin, in collaboration with Dr. SHI Yun's Lab at the Model Animal Research Center of Nanjing University, made serial chimeric GluK1-GluK2 receptors based on their conserved structures. The study was published in Nature Communications.

Researchers applied electrophysiological techniques to hippocampal slice cultures to analyze the synaptic responses mediated by these receptors. They unexpectedly found a crucial inhibitory role for the signal peptide in GluK1 trafficking.

Signal peptides are N-terminal residues of newly synthesized secretory or membrane proteins. Generally, they are regarded as "cellular address codes" for intracellular trafficking, localization and secretion.

When GluK1 signal peptide was replaced by that of GluK2, GluK2 signal peptide reversed the previous synaptic trafficking incapability. The resultant GluK1 (SPGluK2) receptor potentiated synaptic responses similar to wild-type GluK2, and this potentiation was suppressed by coexpressed GluK1 signal peptide in the same neurons.

Furthermore, they found that the inhibitory function of GluK1 signal peptide requires the presence of the N-terminal domain, since GluK1 successfully trafficked to synapses and neuronal surfaces if the N-terminal domain was replaced with the corresponding sequences of GluK2.

Biochemical studies revealed that GluK1 signal peptide directly interacts with its N-terminal domain (ATD). Therefore, the researchers proposed a model whereby the cleaved signal peptide, in a trans manner and behaving as a ligand of GluK1, binds to GluK1 ATD and forms an inhibitory complex regulating GluK1 forward trafficking in neurons.

This study has revealed a signal peptide function for glutamate receptor trafficking and uncovered a novel trafficking mechanism for glutamate receptors. It provides the theoretical basis for further study of synaptic transmission and plasticity, as well as the pathological mechanism of related neurological disorders.

The human brain has around 10 billion neurons. The neural synapses are the basic connection units transferring information between them. Neurotransmitters, which are released by presynaptic neurons, diffuse into the synaptic cleft and bind to the corresponding receptors on postsynaptic neurons. By doing so, they regulate neuronal activity and accomplish information transmission. Any deregulation of this process is regarded as a leading cause of neurological disorder.

Credit: 
Chinese Academy of Sciences Headquarters

Shoulder 'brightness' on ultrasound may be a sign of diabetes

image: Images of the shoulder showing reversal of the rotator cuff to deltoid gradient. Image A displays the normal gradient of the deltoid muscle to the supraspinatus tendon. Image B shows reversal of the normal gradient in a type 2 diabetic patient. D: Deltoid, S: Supraspinatus, H: Humerus

Image: 
Radiological Society of North America

CHICAGO - A shoulder muscle that appears unusually bright on ultrasound may be a warning sign of diabetes, according to a study being presented next week at the annual meeting of the Radiological Society of North America (RSNA).

Ultrasound is commonly used to diagnose sources of pain in the shoulder. More than 10 years ago, musculoskeletal radiologist Steven B. Soliman, D.O., from Henry Ford Hospital in Detroit, began noticing a pattern when images of the deltoid muscle, the largest muscle of the shoulder, appeared bright on ultrasound.

"Every time we would ask one of these patients if they were diabetic, they would say 'yes' or they would tell us they were borderline and not taking any medications," Dr. Soliman said.

The observations prompted Dr. Soliman and colleagues at Henry Ford to conduct a study to see if the brightness, or echogenicity, of the shoulder muscle could be predictive of diabetes. The results revealed that by using the echogenicity of the muscle, radiologists were able to predict type 2 diabetes, the most common type of diabetes, in almost nine out of 10 patients. Brightness on ultrasound also was an accurate predictor of pre-diabetes, a condition of abnormally high blood sugar that generally progresses to diabetes without changes in lifestyle.

The researchers said the findings could allow for earlier interventions.

"If we observe this in patients with pre-diabetes and diabetes, we can get them to exercise, make diet modifications and lose weight," Dr. Soliman said. "If these interventions happen early enough, the patients may be able to avoid going on medications and dealing with all the complications that go with the disease."

For the study, Dr. Soliman and colleagues compiled 137 shoulder ultrasounds from patients with type 2 diabetes, including 13 with pre-diabetes. The researchers also obtained 49 ultrasounds from obese patients without diabetes.

The researchers showed the ultrasounds to two musculoskeletal radiologists who were unaware whether the images came from patients with or without diabetes. The radiologists were asked to classify the patients, based on the brightness of their shoulder muscle, into one of three categories: normal, suspected diabetes and definite diabetes. A third musculoskeletal radiologist acted as an arbitrator in the cases where the other two radiologists disagreed.

The results showed that a consensus diagnosis of "definite diabetes" by the radiologists was a powerful predictor of diabetic status. Using the shoulder ultrasounds, the radiologists correctly predicted diabetes in 70 of 79 patients, or 89 percent.

"We weren't surprised that we had positive results because the shoulder muscle on patients with diabetes looked so bright on ultrasound, but we were surprised at the level of accuracy," Dr. Soliman said.

A hyperechoic, or unusually bright-looking, deltoid muscle was also a strong predictor of pre-diabetes. The musculoskeletal radiologists assigned all 13 pre-diabetic ultrasounds to either the "suspected diabetes" or "definite diabetes" categories.

"A lot of the patients weren't even aware that they were diabetic or pre-diabetic," said Dr. Soliman, who noted that this lack of awareness is a major problem in the U.S.

According to the Centers for Disease Control and Prevention (CDC), nearly one in four Americans with diabetes--about 7.2 million people--are unaware they have the disease and are left undiagnosed.

"Also, the CDC states that pre-diabetes affects an astonishing 84.1 million adults, or nearly 34 percent of the adult U.S. population, and an overwhelming 90 percent of these people are completely unaware of their pre-diabetic status and are at a high risk of developing type 2 diabetes," Dr. Soliman said.

The reasons for the brighter-appearing shoulder muscle on ultrasound among patients with diabetes is not completely understood, according to Dr. Soliman, but the researchers suspect it is due to low levels of glycogen in the muscle, a key source of energy for the body that is stored primarily in the liver and muscles. A study of muscle biopsies in patients with diabetes found that muscle glycogen levels are decreased up to 65 percent. Prior research has also shown that the muscles of athletes appear brighter on ultrasound after exercise, when their glycogen stores are depleted.

"It could be that this appearance in people with diabetes and pre-diabetes is related to the known problems with glycogen synthesis in their muscles because of their insulin abnormalities," Dr. Soliman said.

If they see a bright shoulder muscle on ultrasound, radiologists at Henry Ford now put notes in their reports indicating that this observation has been linked to diabetes.

The researchers plan to continue studying the connection between shoulder muscle echogenicity and diabetes with an eye toward quantifying the phenomenon and seeing if it is reversible.

Credit: 
Radiological Society of North America

Explaining a fastball's unexpected twist

video: Two snapshots are taken 20 microseconds apart, soon after a baseball is launched through a smoke-filled chamber.

Image: 
Sakib and Smith

WASHINGTON, D.C., November 18, 2018 -- An unexpected twist from a four-seam or a two-seam fastball can make the difference in a baseball team winning or losing the World Series. However, "some explanations regarding the different pitches are flat-out wrong," said Barton Smith, a professor of mechanical and aerospace engineering at Utah State University who considers himself a big fan of the game.

He and his doctoral student, Nazmus Sakib, are conducting experiments to explain how baseballs move. Sakib and Smith will present their findings at the American Physical Society's Division of Fluid Dynamics 71st Annual Meeting, which will take place Nov. 18-20 at the Georgia World Congress Center in Atlanta, Georgia.

A baseball is asymmetric owing to the figure-eight stitching pattern, and the way a baseball moves through the air depends on the degree and direction of its spin and its orientation when the hand releases it. The Magnus effect, or the force on a spinning object moving through a fluid like air, pushes in the direction that the front of the ball is spinning. So it causes a ball with topspin to drop and a ball with backspin to gain some lift -- enough to slow its fall, but not enough to overcome gravity.

This well-studied phenomenon affects most pitches except for the virtually spin-free knuckle ball, which is gripped with the thumb and fingertips. The two-seam fastball, which is gripped by the middle and index fingers along the seams, seemed to also behave in a way not explained by the Magnus effect.

Sakib and Smith focus on these two pitches, which are influenced by forces other than the Magnus effect. In their study, the researchers set up a pitching machine that hurls fastballs and knuckleballs through a smoky path. Automatic photographs, triggered by laser sensors, captured two images of the ball and smoke after release. Then, using a technique called particle image velocimetry, Sakib and Smith tracked the movements of the smoke particles to compute the velocity field around the ball and the direction of the rotating air at a given spot.

Then, they computed the "boundary layer separation" by identifying the portions of the ball's surface where the layer of air surrounding the ball had separated to form the wake. While the boundary layer separation varies differently for the two fastball pitches as the ball rotates, the net effect is the same.

Sakib and Smith found that the two-seam pitch has a tilted spin axis due to the fact that one finger leaves the seam before the other, which can cause the ball to move sideways, unlike a four-seam fastball. In the case of the knuckleball, the point of separation can change midflight, causing the ball to randomly shift directions.

Smith is now "hoping to meet a major league pitcher who wants to use what we've learned through fluid dynamics to throw a better pitch."

Presentation E17.1, "Velocity fields of pitched baseballs using Particle Image Velocimetry" by Nazmus Sakib and Barton Smith, will be Sunday, Nov. 18, 5:10 p.m. in Room B304 of the Georgia World Congress Center in Atlanta. Abstract: http://meetings.aps.org/Meeting/DFD18/Session/E17.1

Credit: 
American Physical Society

Sucking your baby's pacifier may benefit their health

video: Eliane Abou-Jaoude, M.D., a Henry Ford Health System allergist fellow and the study's lead author.

Image: 
Henry Ford Health System

DETROIT - Many parents probably think nothing of sucking on their baby's pacifier to clean it after it falls to the ground. Turns out, doing so may benefit their child's health.

A Henry Ford Health System study found that babies whose parents sucked on their pacifier to clean it had a lower level of the antibody that is linked to the development of allergies and asthma.

Researchers theorize parents may be passing healthy oral bacteria in their saliva that will affect the early development of their child's immune system.

The study is being presented at the American College of Allergy, Asthma and Immunology meeting in Seattle.

"Although we can't say there's a cause and effect relationship, we can say the microbes a child is exposed to early on in life will affect their immune system development," says Eliane Abou-Jaoude, M.D., a Henry Ford allergist fellow and the study's lead author.

"From our data, we can tell that the children whose pacifiers were cleaned by their parents sucking on the pacifier, those children had lower IgE levels around 10 months of age through 18 months of age."

The retrospective study is believed to the first of its kind in the United States to evaluate the association between pacifier cleaning methods and the antibody Immunoglobulin E, or IgE. IgE is linked to the development of allergies and asthma. The findings are compatible with those from a 2013 Swedish study, which reported an association between parents sucking on their baby's pacifier with a reduced risk of allergy development.

The Henry Ford study involved 128 mothers who were asked about how they cleaned their baby's pacifier: Sterilizing it in boiling water or dishwasher, cleaning it with soap and water and sucking on it. Among the three methods, 30 mothers sterilized it, 53 cleaned it with soap and water and nine sucked on the pacifier.

Researchers compared the babies' IgE levels at birth, six months and 18 months for each cleaning method, and found a "significantly lower level IgE level for babies at 18 months" whose mothers sucked on the pacifier to clean it. Additional analyses indicated the differences were first seen at about 10 months.

Dr. Abou-Jaoude cautions parents from concluding that sucking on their baby's pacifier to clean it will lower their child's risk of developing allergies. More research is needed to examine that potential correlation, Dr. Abou-Jaoude says.

Credit: 
Henry Ford Health

A new lead on a 50-year-old radiation damage mystery

ANN ARBOR--For half a century, researchers have seen loops of displaced atoms appearing inside nuclear reactor steel after exposure to radiation, but no one could work out how.

Now, a simulation done by researchers at the University of Michigan, Hunan University (China) and Rensselaer Polytechnic Institute has shown that a shockwave produces these loops in iron. The result could help engineers design better radiation-resistant steel for reactors--or stronger steel in general.

Iron and steel, like most metals, organize themselves in a crystal lattice--an arrangement of atoms based on a repeated pattern. In this case, it's a cube with an atom at each corner and one in the center. Radiation and other stresses can create a variety of defects.

In "loop" defects, the out-of-place atoms form rough rings. Some loops can travel through the lattice, and their mobility means that they don't get in the way of the steel bending. But the defect in question (known as a interstitial dislocation loop) tends to stay put. Placed in an uncontrolled way, these stationary loops cause brittleness, but if they were placed deliberately, they could strengthen steel by improving its stiffness.

"Now that we know the mechanism, we can reduce radiation damage by limiting the energy of the particles that materials are exposed to," said Qing Peng, a research fellow in the lab of Fei Gao, a professor of nuclear engineering and radiological sciences.

"We can also use it to engineer the defect inside materials. Depending on the energy, you can generate different types of dislocations to tune the material's properties."

Five earlier explanations are in the running to account for the mysterious loops, but none is particularly satisfying because they all require special conditions and relatively long times to create the loops.

Since the defects appear too quickly to measure, researchers expected that they would be able to simulate the mechanism on a computer. But that didn't happen either. They supposed that it took too long to map out their real time trajectories--there just wasn't enough power to simulate all those atoms in a reasonable time.

That last observation turned out to be partially true: there were too many atoms to model. But the process itself was short; the trouble was making the volume of iron big enough to get the reaction.

"If the simulation is too small, a high-energy particle just passes through. No reaction," Peng said.

Gao's team created a computer model of a box of 200 million iron atoms, arranged in the typical lattice, and slammed a high energy particle into it. What they saw was a powerful shockwave ripping through the lattice, branching out in different directions.

Millions of iron atoms were displaced from their spots, and millions of them fell back into the lattice as the wave dissipated. Left behind were hundreds of "point" defects in which single atoms were out of place--and a handful of loops. Many of these were loops that can travel, which aren't a major cause of brittleness, but often one or two were the stationary type.

It turned out that the loops were created in the initial shockwave, a process that takes just 13 trillionths of a second or so. This explanation was floated as early as 40 years ago, but it was used to explain defects that appeared in lines rather than closed loops.

Now that the mechanism is known, similar computer modeling may be used to recommend operating conditions for steel alloys in environments with radiation. Less energetic particles won't create shockwaves strong enough to produce this defect.

Or, defects like this can be deliberately placed in steel to enhance its rigidity. These stationary loops of atoms, jammed in between other atoms in the crystal, make it harder for steel to bend.

Credit: 
University of Michigan

Dodging antibiotic resistance by curbing bacterial evolution

image: Mark N. Ragheb, an M.D./Ph.D. student at the University of Washington School of Medicine, is the lead author of a Molecular Cell paper on the search for anti-evolution drugs to combat antimicrobial resistance in disease bacteria

Image: 
Houra Merrikh/UW Medicine

With many disease-causing bacteria ratcheting up their shields against current drugs, new tactics are vital to protect people from treatment-resistant infections.

Lowering mutation rates in harmful bacteria might be an as yet untried way to hinder the emergence of antimicrobial-resistant pathogens. This proposed strategy comes from recent findings in infectious disease research at UW Medicine in Seattle.

The report on this work is published this week in Molecular Cell, one of the journals of Cell Press. The lead author is Mark N. Ragheb, an M.D./Ph.D. student at the University of Washington School of Medicine. The senior researcher is Houra Merrikh, associate professor of microbiology at the UW medical school.

While most efforts against antimicrobial resistance concentrate on producing better antibiotics, the scientists note, "History shows that resistance arises regardless of the nature or potency of new drugs."

Deaths from antibiotic-resistant infections, they explain, have reached alarming numbers worldwide, and show signs of surpassing mortality from other causes by mid-century.

In looking for another approach to combating this public health threat, the team of microbiologists, genome scientists, pathobiologists and molecular and cellular biologists found evidence for a key promoter of mutations in many different bacteria. This protein factor, DNA translocase Mfd, seems to speed resistance in diverse species toward every antibiotic that was tested.

The researchers call bacterial proteins like Mfd "evolvability factors" because, by increasing mutation rates, they propel the evolution of bacteria. Unlike many multicellular organisms, bacteria evolve quickly. This allows their species to survive or escape suddenly changing conditions, scarcity of nutrients and hostile environments -- including attempts to destroy them with antibiotics or immune responses.

Many types of bacteria produce Mfd, an indication of its important physiological role in cells. While it was once thought to assist in DNA repair, cells missing it are not more sensitive to DNA damaging agents. Those with too much of it are actually more prone to DNA damage.

In studying what is behind trimethoprim resistance, for example, the researchers saw that potent, alternative genes that accelerate antibiotic resistance failed to crop up when Mfd was absent. In certain wild type strains of bacteria with Mfd that were studied, those that gained these so called hypermutator alleles had a mutation rate that was more than 1,000 times that of their ancestral strain.

The researchers estimated that roughly half of the strains under study developed hypermutator alleles during the course of becoming resistant to trimethoprim. These strains also accumulated a high number of mutations across their genomes. Strains lacking Mfd were unlikely to form these hypermutator alleles.

The researchers noted, "Generating hypermutation may offer an adaptive strategy to evolve high-level antibiotic resistance, and Mfd might promote this phenomenon."

In other aspects of their project, the scientists reported that Mfd depends on certain other proteins that work on the bacteria's genetic machinery in order to carry out its job in antibiotic resistance. Mdf's role also might possibly be enhanced or even exaggerated during bacterial infections of living things, in comparison to what happens when these bugs live in lab dishes.

Also, the data acquired in this research project seem to show that the role of Mfd in increasing mutations and promoting antibiotic resistance is highly conserved across bacterial species, and is not specific to only a few types of pathogens.

Among the several pathogens studied, the researchers were particularly interested in the mycobacterium that causes tuberculosis. They discovered what they describe as a "striking" difference in resistance to a representative antibiotic -- rifampicin -- in strains with and without Mfd.

The finding that Mfd is critical to the development of antibiotic resistance in mycobacterium TB could have potential clinical implications, the researchers noted.

Exactly how Mfd encourages mutations and antibiotic resistance is still unclear. One explanation put forth is that it sets the stage for error-prone repair of DNA, even at sites without damage. Or it could interfere with other biochemical pathways for fixing DNA.

The evolutionary assays in this study tried to mimic the variable concentrations of antibiotics that are common during treatment of infections in patients. It's possible that Mfd may play a role in producing high levels of antibiotic resistance when bacteria are first exposed to antibiotics in amounts that are not enough to stop them.

The researchers also think that Mfd's ability to promote multiple mutations may be significant in the development of multi-drug resistance.

Based on their findings, the researchers concluded, "We propose that blocking evolvabilty factors, in particular Mfd, could be a revolutionary strategy to address the antimicrobial resistance crisis."

A new class of anti-evolution drugs that target Mfd or other evolvability factors that promote mutations may complement new antimicrobials and alleviate the problem of chromosomally acquired mutations that leads to antimicrobial resistance.

They added that, in principle, drugs designed to target Mfd could be co-administered with antibiotics during treatment of infections. That might reduce the likelihood of resistance developing at the start of therapy.

Beyond the importance of reducing antibiotic resistance, there could be even wider implications of understanding and intervening in the evolutionary capacity of cells, according to the researchers. These include restraining genetic changes in cancer cells, and limiting the diversity in the strains of a pathogen a person's immune system is trying to overcome.

Supplemental drugs, such as the proposed evolution inhibitors, could, the researchers predict, improve the efficiency and effectiveness of current treatments, and thereby expand the arsenal of drugs available to combat antimicrobial resistant infections, cancers, and other diseases.

Credit: 
University of Washington School of Medicine/UW Medicine

Color coded -- matching taste with color

image: Representation of colored stimuli used in conditioning trials

Image: 
Molly Higgins / Penn State

Color can impact the taste of food, and our experiences and expectations can affect how we taste food, according to Penn State researchers, who suggest this may have implications for how food and beverage industries should market their products.

"The color of a beverage can impact how we think it should taste," said John E. Hayes, associate professor of food science and director, Sensory Evaluation Center, Penn State. "For example, yellow is commonly associated with drinks that are more sour, like lemonade, whereas red is associated with drinks that are more sweet, like sports drinks."

The Penn State researchers wondered how people learn color-taste associations, and whether people could be taught new color-taste associations. They reported their findings online in Food Quality and Preference, and it will be published in the January print edition.

Also, the researchers wanted to determine why people enjoy the bitter taste in some foods but not others.

"Bitterness can indicate toxicity, but people still enjoy coffee, chocolate and IPA-style beers," said Molly J. Higgins, doctoral candidate in food sciences. "Why do people like some bitter compounds but not others?"

Hayes and Higgins wanted to find out if there were differences between different bitter compounds, and if people could taste those differences. If there are different types of bitter tastes, it could explain why some people like the bitterness of coffee, but not the bitterness of chocolate.

"There may be different kinds of bitterness, even if we don't have the language to describe it," said Hayes.

First, Hayes and Higgins needed to test whether they could teach people to associate specific tastes with specific colors. They created solutions that tasted bitter, sweet, sour or savory, and paired each one with a unique color, such as green for sweet or red for bitter.

"We avoided preconceived color-taste pairings, such as yellow for sour or red for sweet, because we didn't want to bias our sample," said Higgins.

The researchers had participants taste the colored liquids over four different sessions, then gave the participants uncolored solutions and asked them to taste and choose a color for each.

Participants matched the correct color and taste 59 percent of the time, significantly higher than the researchers expected from random chance, which would have been 25 percent. It surprised researchers how quickly some participants learned to associate new colors with different tastes.

"This was only after four exposures," said Higgins. "We were surprised to see some participants correctly match every sample in the post test."

After showing that they could teach new color-taste associations to their participants, researchers then tested whether people could distinguish between three different bitter tastes -- caffeine, quinine, and Tetralone, a hop extract found in beers. Hayes and Higgins repeated the experiment with a new group of study subjects and assigned unique colors to each bitter chemical, such as yellow for caffeine and green for quinine. However, after four lab visits, participants could not match the colors to their corresponding bitter compounds any better than expected by chance.

Although the research did not get the results they expected, they still were intrigued by how quickly some participants learned new color-taste associations in the first experiment. Hayes and Higgins continue to study how people associate taste with color, noting that while some participants were quick learners, others were not.

"This finding could indicate that some people learn color-taste associations well, while others might be more resistant to changes or new color-taste associations," said Higgins. "This might have implications in the food industry if a company were to launch a new flavored product with a color. Some consumers might not learn or accept a new color and flavor pairing as well as others."

Credit: 
Penn State

Majority of HIV persistence during ART due to infected cell proliferation

SEATTLE -- Nov. 16, 2018 -- A majority of the HIV-infected cells that persist in HIV-infected individuals even during suppressive antiretroviral therapy (ART) originated from cellular proliferation, not viral replication, according to new research published in Nature Communications.

Reducing the population size of this "reservoir" of infected cells represents the largest challenge for cure of HIV. Based on these results, study authors believe reducing cellular proliferation could help to deplete the reservoir and potentially lead to a functional cure.

Led by Drs. Dan Reeves and Josh Schiffer in the Vaccine and Infectious Diseases Division at Fred Hutchinson Cancer Research Center, the research team combined mathematical models and immunological insight to understand how the genetic signature of HIV-infected cells could explain their origin.

"Our approach was inspired by ecology," said Dr. Reeves, the study's first author and research associate in the Vaccine and Infectious Disease Division at Fred Hutch. "We adapted tools to characterize the reservoir of HIV-infected cells more realistically, inferring the mechanism of generation from the proportions of unique and identical genetic signatures."

When HIV infects a healthy cell, it inserts its own DNA into the human chromosome, leaving behind a unique genetic signature. If the virus replicating itself were the cause of latent HIV reservoirs, the study authors suggest, this genetic signature would contain unique integration sites and different mutations in the DNA of infected cells.

In fact, they found a majority of genetic signatures were identical, indicating that persistence within HIV reservoirs is the product of normal CD4+ T-cell mitosis. Both to maintain a stable population of cells and in response to foreign antigens, CD4+ T cells routinely undergo proliferation every few months. HIV DNA is copied into daughter cells along with human DNA each time this normal process occurs.

ART has been an effective tool in helping HIV-positive individuals live healthy lives since the late 1990s. HIV researchers have since been working to understand why reservoirs of HIV-infected immune cells remain at low levels during ART treatment, and how to identify and purge infected cells. The study authors believe that reducing proliferation of specific immune cells, CD4+ T cells, could greatly deplete HIV reservoirs and potentially lead to a functional HIV cure. Possible approaches for depleting the infected cells might be gene editing, cellular immunotherapy or latency reversing agents.

Dr. Schiffer, senior author of the study and Associate Member in the Vaccine and Infectious Disease Division at Fred Hutch commented, "We see parallels in achieving functional cures in both HIV and cancer; for example, the difficulties of remission and relapse, and how combination therapies could be successful in bringing either disease to undetectable levels in the body."

Schiffer and colleagues are conducting a clinical trial to test whether the lymphocyte anti-proliferative drug mycophenolate mofetil (MMF) could be effective at stopping the proliferation of HIV-infected immune cells in people undergoing ART. MMF is already licensed for use in preventing graft-vs.-host disease following stem cell transplant and reducing the risk of rejection after organ transplant. Schiffer refers to this approach of adjusting the rate of division as a "compound interest cure," which, if successful, could significantly deplete or eliminate latent HIV reservoirs.

Credit: 
Fred Hutchinson Cancer Center

Caregiver's poor knowledge of asthma means longer hospital stay for child

SEATTLE (November 16, 2018) - Asthma is a complex disease, and it can be a challenge to keep up with your child's medications and treatments. New research being presented at the American College of Allergy, Asthma and Immunology (ACAAI) Annual Scientific Meeting shows children of caregivers with poor asthma knowledge were four times more likely to have a prolonged hospital stay. A "prolonged" stay was defined as more than two days.

"We studied 72 children ages 2-17 who had been hospitalized with asthma," says allergist Deepti Deshpande, MD, MPH, ACAAI member and lead author on the study. "Their caregivers completed a questionnaire when their child was admitted, when they were discharged and again four to six weeks after discharge. If the caregiver had poor asthma knowledge when their child was admitted, the odds were four times greater that the child's length of hospital stay would be longer than two days. If caregiver asthma knowledge was good, the odds were strong that the child's hospital stay would be less than two days."

Asthma education during the hospital stay for children and their families included interactive material that covered general asthma knowledge as well as asthma triggers and ways to control them. During their child's stay, caregivers were given demonstrations on correct inhaler technique and learned how to use an asthma action plan.

"We focused on providing families with a better understanding of medications, their use, side effects and correct technique for use of devices to help improve use," says Dr. Deshpande. "After the education program, caregivers showed an increase in their general asthma knowledge from admission, to four to six weeks after discharge. Additionally, at 4-6 weeks after discharge, 90 percent of caregivers were able to correctly name their child's rescue medicine and 73 percent were correctly able to name the controller medicines."

Many people aren't aware that allergists can work with you and your child to bring asthma under control and reduce symptoms. Allergists are specially trained to help you take control of your asthma, so you can live the life you want.

Credit: 
American College of Allergy, Asthma, and Immunology

Eyeing echidnas

These days, mammals can use their forelimbs to swim, jump, fly, climb, dig and just about everything in between, but the question of how all that diversity evolved has remained a vexing one for scientists.

To help answer it, Harvard researchers are turning to one of the most unusual mammals around - echidnas. These sprawling, egg-laying mammals have many anatomical features in common with earlier mammal ancestors, and so can help bridge the gap between extinct and other modern-day mammals.

Using a highly-detailed musculoskeletal model of an echidna forelimb, Sophie Regnault, a Post-Doctoral Fellow and Stephanie Pierce, Associate Professor of Organismic and Evolutionary Biology, were able to not only shed more light on how the little-studied echidna's forelimb works, but also open a window into understanding how extinct mammals might have used their forelimbs. The model is described in a November 14 paper published in Royal Society Open Science.

"Echidnas are not very well-studied, and little is known about their biomechanics." Regnault says. "There are few related species, and echidnas themselves can be difficult to study because they have very large spines hiding underlying movements. We made this virtual model using CT scans that allow us to look in closer detail at how the skeleton and muscles interact with one another."

The researchers discovered that the bony anatomy and muscles work together to optimize limb leverage and mobility for certain kinds of movements. In particular, the configuration of muscles support limb rotation important for the echidna's sprawling gait.

"This model gives us unique insight into not only the echidna but can also guide reconstructions of extinct mammals," Pierce says. "The similarities between the echidna forelimb skeleton and transitional animals can help us to understand the evolution of forelimb diversity in modern mammals."

"If we find certain muscles have lots of leverage, it might suggest that certain postures or types of movement are more likely," Regnault add. "We're continuing to add data to our echidna model, and one thing we're hoping to do is to understand how things like mobility and leverage can be used to predict how an animal might have stood or what kind of movements it could have made."

"This study is part of a much larger project," Pierce says. The researchers' ultimate goal is to reconstruct the evolution of the mammal forelimb by building similar models for fossils at key stages. The echidna model is a first step in understanding the relationships between form and function of the forelimb.

By looking at how the mammal forelimb changed through time, they hope to reveal how modifications to the skeleton led to the ecological and behavioral diversity we see today.

Credit: 
Harvard University

Selling plants on Amazon: A forest of untapped opportunity

A first-of-its-kind study out of Kansas State University examined the the untapped market for selling plants online by horticultural businesses.

Lauri Baker, Cheryl Boyer, Hikaru Peterson, and Audrey King researched this facet of the $14 billion US horticulture industry to establish a starting point for ongoing examination of this relatively new entrepreneurial phenomenon in their article, "Online Opportunities: A Quantitative Content Analysis Benchmark Study of Online Retail Plant Sales," as found in the journal HortTechnology.

Researchers noted that the US horticultural industry faces numerous challenges to maintaining successful, independently owned retail businesses. Among those challenges are that horticultural businesses face heightened competition and rely primarily on inefficient methods and avenues for self-promotion, such as phone books, catalogs, and newspaper ads.

Today's customers increasingly use modern electronics and search engines before committing to purchasing decisions, and therefore remain aloof to the majority of the promotional efforts of horticultural businesses.

"A high-quality online presence is essential for the viability of horticultural businesses," the study's authors said. "Lack of modernization, however, coupled with often limited resources for developing online content, have resulted in slow adoption of new sales technology in small to medium enterprises, such as garden centers, nurseries, and other horticultural businesses."

The study surmises that one way small, independently owned horticultural businesses can potentially succeed is by expanding their use of e-commerce. Within this article, the researchers examined the practice of using online-shopping websites for retail sales directly to the customers, often selling through online marketplaces such as Amazon and eBay. Amazon is the largest provider in the United States for online direct sales and has already accounted for the growth of numerous other types of businesses venturing into the online marketplace.

But the research indicates the adoption of online services by the horticultural industry is incomplete. Boyer says, "This is not surprising, as our previous research with garden center owners and employees demonstrated a need for more education on the use of online marketing tools for their businesses, leading us to create The Center for Rural Enterprise Engagement."

From a consumer perspective, multiple factors influence the decision to purchase a product online, such as return policy, product quality, price strategy, on-time delivery, terms of sale, pictures on the website, shipping charges, and selection. No previous studies have looked at how these characteristics translate to horticultural businesses.

The researchers discovered that selling plants on Amazon can be challenging. Amazon does not allow website copy (descriptions of the plants) to link to the seller's own e-commerce site. In addition, seller requirements are strict, particularly when participating in the Amazon Prime two-day shipping service, which can be difficult when shipping live plants. Also, the pricing model for professionals contains a series of cost-prohibitive fees that could dissuade struggling horticultural businesses. In spite of these findings, Amazon's presence in the live plant marketplace has increased at a rapid pace in recent years. However, the focus of these sales and deliveries has been mainly in major metropolitan areas.

The purpose of this study was to determine the extent to which horticultural businesses were directly selling live plant products online, either through Amazon or from their own websites. The sample selected for this study consisted of 498 businesses with current membership in a national association for the horticultural industry, including breeders, greenhouses and nursery growers, retailers, distributors, interior and exterior landscapers, florists, students, educators, researchers, and manufacturers.

Of these 498 participants in this study, only four were already engaged in the practice of selling live plant products through Amazon, while 44 businesses were selling online through their own websites with a fully functioning shopping-cart tool.

It is clear the majority of horticultural businesses have not yet adopted the practice of selling live plants online and that the industry is in the early stages of using this technology for commercial benefit. While the sample of businesses using online sales was too low to draw sufficient useful conclusions, it appears that most horticultural businesses are struggling to meet the current expectations of online customers.

Credit: 
American Society for Horticultural Science

Overflowing crater lakes carved canyons across Mars

image: Jezero crater is a paleolake and potential landing site for NASA’s Mars 2020 rover mission to look for past life. The outlet canyon carved by overflow flooding is visible in the upper right side of the crater. Ancient rivers carved the inlets on the right side of the crater.

Image: 
NASA/Tim Goudge.

Today, most of the water on Mars is locked away in frozen ice caps. But billions of years ago it flowed freely across the surface, forming rushing rivers that emptied into craters, forming lakes and seas. New research led by The University of Texas at Austin has found evidence that sometimes the lakes would take on so much water that they overflowed and burst from the sides of their basins, creating catastrophic floods that carved canyons very rapidly, perhaps in a matter of weeks.

The findings suggest that catastrophic geologic processes may have had a major role in shaping the landscape of Mars and other worlds without plate tectonics, said lead author Tim Goudge, a postdoctoral researcher at the UT Jackson School of Geosciences who will be starting as an assistant professor at the school in 2019.

"These breached lakes are fairly common and some of them are quite large, some as large as the Caspian Sea," said Goudge. "So we think this style of catastrophic overflow flooding and rapid incision of outlet canyons was probably quite important on early Mars' surface."

The research was published Nov. 16 in the journal Geology. Co-authors include NASA scientist Caleb Fassett and Jackson School Professor and Associate Dean of Research David Mohrig.

From studying rock formations from satellite images, scientists know that hundreds of craters across the surface of Mars were once filled with water. More than 200 of these "paleolakes" have outlet canyons tens to hundreds of kilometers long and several kilometers wide carved by water flowing from the ancient lakes.

However, until this study, it was unknown whether the canyons were gradually carved over millions of years or carved rapidly by single floods.

Using high-resolution photos taken by NASA's Mars Reconnaissance Orbiter satellite, the researchers examined the topography of the outlets and the crater rims and found a correlation between the size of the outlet and the volume of water expected to be released during a large flooding event. If the outlet had instead been gradually whittled away over time, the relationship between water volume and outlet size likely wouldn't hold, Goudge said.

In total, the researchers examined 24 paleolakes and their outlet canyons across the Red Planet. One of the paleolakes examined in the study, Jezero Crater, is a potential landing site for NASA's Mars 2020 rover mission to look for signs of past life. Goudge and Fassett proposed the crater as a landing site based on prior studies that found it held water for long periods in Mars' past.

While massive floods flowing from Martian craters might sound like a scene in a science fiction novel, a similar process occurs on Earth when lakes dammed by glaciers break through their icy barriers. The researchers found that the similarity is more than superficial. As long as gravity is accounted for, floods create outlets with similar shapes whether on Earth or Mars.

"This tells us that things that are different between the planets are not as important as the basic physics of the overflow process and the size of the basin," Goudge said. "You can learn more about this process by comparing different planets as opposed to just thinking about what's occurring on Earth or what's occurring on Mars."

Although big floods on Mars and Earth are governed by the same mechanics, they fit into different geological paradigms. On Earth, the slow-and-steady motion of tectonic plates dramatically changes the planet's surface over millions of years. In contrast, the lack of plate tectonics on Mars means that cataclysmic events -- like floods and asteroid impacts -- quickly create changes that can amount to near permanent changes in the landscape.

"The landscape on Earth doesn't preserve large lakes for a very long time," Fassett said. "But on Mars ... these canyons have been there for 3.7 billion years, a very long time, and it gives us insight into what the deep time surface water was like on Mars."

Credit: 
University of Texas at Austin

Newborn babies' brain responses to being touched on the face measured for the first time

A newborn baby's brain responds to being touched on the face, according to new research co-led by UCL.

Babies use this sense of touch - facial somatosensation - to find and latch onto their mother's nipple, and should have this ability from birth.

Premature babies often have difficulty feeding, and underdevelopment of their facial sensitivity may be one of the main causes.

Researchers from UCL, Imperial College London, UCLH and Universitá Campus Bio-Medico di Roma developed a new method to study this sense of touch in babies and how their brains reacted using electroencephalography (EEG).

Current methods of evoking brain activity in response to touch aren't suitable for a newborn's face, so academics have developed a device - based on a transducer - worn on the fingertip, covered by a clinical glove.

The baby can be lightly tapped on the cheek, and then brain responses are measured as well as the force of the tapping.

The report, 'A novel sensor design for accurate measurement of facial somatosensation in pre-term infants', is published in the journal PLOS ONE.

Dr Lorenzo Fabrizi (UCL Biosciences) said: "This research provides a way of understanding how pre-term babies process touch information, and could help medical professionals to make informed decisions relating to their development.

"We've proved that we can record the sense of touch from the face. This means that for premature babies, it is possible to study how they process the tactile information that they receive from the face, how this changes as they mature and whether disruption of this process might lead to longer-term feeding problems."

Babies' brains develop quicker than at any other point in life. Facial somatosensation is necessary for breastfeeding; for example if a newborn baby's right cheek is lying on their mother's breast, the baby uses this information to turn its head to the right in order to feed (rooting). Therefore finding a way to measure brain responses to facial touch is important for understanding brain development in newborns.

Professor Etienne Burdet (Imperial College London) said: "We had to develop a stimulating system that was safe to use on the delicate face of the babies and acceptable to their parents. We used an iterative design approach to develop a seamless wearable device that can measure a natural finger tap to the skin.

"After we found that conventional sensors were not practical, we developed a dedicated sensor and packaging using 3D printing."

The study looked at seven babies who were on average seven days old at UCLH's postnatal and neonatal wards, each one having been born prematurely (before 37 weeks).

The research was supported by the UK Medical Research Council, European Commission grants, and a UK EPSRC MOTION grant. The force transducer was developed at Imperial College London and the trial was carried out at UCL and the UCLH Elizabeth Garrett Anderson wing. Ethical approval was obtained from the NHS Research Ethics Committee along with informed parental consent for each baby.

Credit: 
University College London

Organizations with broad social ties help recovering from natural disasters

BUFFALO, N.Y. - Communities recovering from natural disasters often see an increase in the number of businesses and non-profits that develop in the wake of the cleanup, but that apparent growth doesn't necessarily counterweigh the accompanying rise in poverty levels in areas transformed by events such as storms, earthquakes and wildfires.

These emerging businesses can improve the economic well-being of post-disaster communities, but what's true for businesses is not always the case for other types of community organizations, according to the results of a new study by a University at Buffalo-led research team.

"We found that community organizations, like churches, that are focused on their own needs during disasters do not block out the increase in poverty rates," says Kevin Smiley, an assistant professor of sociology at UB and the paper's lead author. "These organizations are an important part of the recovery and are effective on a small scale, but counties with increasing numbers of advocacy organizations, such as local environmental groups, political organizations and human-rights groups, tend to have a better recovery in terms of economic inequality."

The findings suggest that the most equitable recoveries are in those places where organizations that have a broad, crosscutting presence are located, and Smiley says that in order to encourage a wide economic recovery, communities should think about activating advocacy organizations that reach across diverse populations.

"In California, after the last of the fires has been put out, and the affected communities come together in their recovery, these broad-based organizations can help in a more equitable disaster recovery - it's not just the economic; it's the social," says Smiley. "Governments are uniquely positioned to help accomplish this. These organizations represent the democratic possibility; they are the institutions in which we imbue our collective spirit and they have the best opportunity to reach people.

"Communities come together following a disaster, but it's a lot to ask of a small isolated organization like a local church when a government already has that megaphone," says Smiley.

One of the curiosities of this research is that every community in the United States can learn from its findings - well, almost every community.

Natural hazards accompanied by property damage - not just headlines-grabbers like hurricanes and floods, but events such as hail, winter weather or severe thunderstorms - have occurred in all but one of the nation's 3,137 counties. Only rural Lyman County in South Dakota was untouched by a damaging event between 1998 and 2015, the timeframe Smiley and his colleagues examined for the study, which was published in the journal Population and Environment.

"These events are happening nearly everywhere in the country," says Smiley. "Given that prevalence, it's important to understand what's happening long-term and how to help communities recover."

The research team, including James Elliott, a professor of sociology at Rice University, and Junia Howell, an urban sociologist at the University of Pittsburgh, was motivated by how people come together after disasters to rebuild and how disasters have uneven impacts, like rising social, income and neighborhood inequalities.

"In the time span we studied, the average U.S. county experienced a total of $100 million in property damage from natural hazards," says Elliott. "This means the growing frequency and severity of natural hazards is an issue that every local community must consider."

The analysis relies on data from the Spatial Hazard Events and Losses Database, a county-level collection of information on damages in the U.S. from natural hazards.

"By looking at all counties in the United States across an 18-year period, this study is able to demonstrate how all places - not just those hit by mega disasters - are being affected by natural hazards and how organizations respond to them," says Smiley.

Credit: 
University at Buffalo

How to successfully motivate California's Medicaid population to quit smoking

Ann Arbor, November 16, 2018 - New research shows improved smoking cessation outcomes can be achieved within the Medi-Cal (California's Medicaid program) population by supplementing telephone counseling with access to nicotine-replacement patches and moderate financial incentives that are not contingent on outcomes. The group that received these additional services was more likely to make a quit attempt and remain smoke-free, both short- and long-term. This study also adds to the evidence that modest financial incentives can be an effective smoking cessation intervention for a low-income population.

This research was published in a special supplement to the American Journal of Preventive Medicine, guest edited by Steven A. Schroeder, MD, Department of Medicine, Smoking Cessation Leadership Center, University of California, San Francisco, CA, USA, which describes components of California's Medi-Cal Incentives to Quit Smoking (MIQS) Project, its successes, and ongoing initiatives.

Key points:

The MIQS Project produced impressive increases in motivating low-income smokers to call and enroll in quitline services and modest, but significant increases in quit attempts and successful quits.

There was a 70 percent increase in calls to the quitline by Medi-Cal smokers, achieving a quitline reach of 4.5 percent, which exceeds the national quitline reach of 1 percent.

Smokers assigned to the nicotine patch plus financial incentive group were more likely to make a quit attempt than the usual care (counseling-only group) and more likely to report six-month prolonged abstinence.

The MIQS Project also demonstrated that offering nicotine patches plus a financial incentive to Medi-Cal smokers who call the quitline is cost-saving.

In a study of statewide outreach for the MIQS Project, led by Elisa K. Tong, MD, of the Department of Internal Medicine, University of California, Davis, Sacramento, CA, USA, promotion through health care channels increased the utilization and reach of quitline services to maximum levels. "Healthcare channels were an important referral source, as more Medi-Cal callers than non-Medi-Cal callers cited providers and plans rather than media," Dr. Tong observed. "MIQS may be sustained with coordination and prioritization across plans, providers, and public health partners."

Researchers conducted a randomized controlled trial to assess which approach was most helpful in getting Medicaid smokers to quit. They randomly assigned participants to one of three groups: usual care, consisting of smoker quitline counseling and assistance in obtaining quitting aids through Medicaid; usual care plus nicotine patches mailed directly to participants' homes, and usual care plus mailed patches and financial incentives of up to $60 per person. Compared to usual care, people offered nicotine patches and financial incentives were more likely to:

Make a quit attempt (68.4 percent vs. 54.3 percent)

Be abstinent for 30 days at 2 months (30.0 percent vs.18.9 percent)

Six-month prolonged abstinent at 7 months (13.2 percent vs. 9.0 percent)

Medicaid expanded eligibility under the 2010 Affordable Care Act, increasing the population of smokers on Medi-Cal. An analysis of datasets from the California Health Interview Survey led by Shu-Hong Zhu, PhD, of the Department of Family Medicine and Public Health, University of California, San Diego, CA, USA, showed that between 2012 and 2016, the number of smokers in California's Medi-Cal program nearly doubled from 738,000 in 2011-2012 to 1,448,000 by 2016, raising the proportion of state smokers covered by Medi-Cal from 19.3 percent to 41.5 percent. Compared with smokers with private insurance, those in Medicaid were more likely to have chronic disease and experience severe psychological distress. In 2016, 51.4 percent of adult smokers with chronic disease conditions and 57.8 percent of those in severe psychological distress were covered by Medi-Cal.

"The growing concentration of smokers in Medicaid highlights the need for more effective approaches to reduce smoking in this population," said Dr. Zhu. "I hope this study captures the attention not just of public health officials, but also of their counterparts in Medicaid. Reducing the toll of tobacco in this population should become an urgent priority for all Medicaid programs and plans."

In a cost-benefit analysis that assesses the economic impact of supplementing usual care of quitline services with mailed nicotine patches and financial incentives of up to $60 per person, investigators found that compared to usual care alone, offering these adjunctive services to Medicaid callers will reduce future healthcare expenditures due to increased number of quitters. This will produce a net savings within five years with a benefit-cost ratio of 1.18. The net savings will accumulate over time with a benefit-cost ratio of 1.90 over 10 years.

"Our study demonstrates that investment in an effective smoking cessation intervention for Medicaid smokers can reap large savings down the road," stated Hai-Yen Sung, PhD, of the Institute for Health & Aging, School of Nursing, University of California, San Francisco, CA, USA. "Providing modest financial incentives and mailed nicotine patches to Medicaid smokers who call the quitline is cost-saving. For every $1 invested in these adjunctive services to Medicaid callers, there will be $1.90 savings in healthcare costs within 10 years."

This research is part of a five-year, $10 million grant awarded to the Department of Health Care Services (DHCS) by the Centers for Medicare & Medicaid Services (CMS) in 2011 and was part of an initiative exploring the use of incentives to change health behaviors in the Medicaid population. This research was designed to accelerate successful quitting by: increasing use of a well-established and effective phone counseling service, the California Smokers' Helpline (CSH); decreasing barriers to obtaining nicotine replacement patches; and offering economic incentives to encourage quitting.

Led by the Department of Health Care Services, collaborators included the University of California San Diego (where the Helpline was developed and is currently housed); University of California Davis; University of California San Francisco; and the California Department of Public Health. This strategy was based on evidence showing that quitlines do improve the chances of quitting and that Medicaid smokers are motivated to quit, although their quit rates are somewhat lower than the general population.

"There is no single magic bullet to reduce the burden of smoking. The results of individual efforts, such as general or targeted mailings, free nicotine replacement therapy, referral to telephone quitlines, and financial incentives (all used in MIQS), as well as taxation, smoke-free legislation, and counter-marketing (all occurring in California as a backdrop to MIQS) may be relatively modest, but each contributes to driving down smoking rates. In the case of California, even a small percentage drop in smoking, when applied to almost 1.5 million Medicaid smokers, could save thousands of lives and millions of dollars," concluded Dr. Schroeder.

Credit: 
Elsevier